Ostrowski Lauren A, Hall Amanda C, Mekhail Karim
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1M1, Canada.
Canada Research Chairs Program, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Genes (Basel). 2017 Jun 5;8(6):157. doi: 10.3390/genes8060157.
RNA-binding proteins play fundamental roles in the regulation of molecular processes critical to cellular and organismal homeostasis. Recent studies have identified the RNA-binding protein Ataxin-2 as a genetic determinant or risk factor for various diseases including spinocerebellar ataxia type II (SCA2) and amyotrophic lateral sclerosis (ALS), amongst others. Here, we first discuss the increasingly wide-ranging molecular functions of Ataxin-2, from the regulation of RNA stability and translation to the repression of deleterious accumulation of the RNA-DNA hybrid-harbouring R-loop structures. We also highlight the broader physiological roles of Ataxin-2 such as in the regulation of cellular metabolism and circadian rhythms. Finally, we discuss insight from clinically focused studies to shed light on the impact of molecular and physiological roles of Ataxin-2 in various human diseases. We anticipate that deciphering the fundamental functions of Ataxin-2 will uncover unique approaches to help cure or control debilitating and lethal human diseases.
RNA结合蛋白在调控对细胞和机体稳态至关重要的分子过程中发挥着基本作用。最近的研究已确定RNA结合蛋白ataxin-2是包括II型脊髓小脑共济失调（SCA2）和肌萎缩侧索硬化症（ALS）等多种疾病的遗传决定因素或风险因素。在此，我们首先讨论ataxin-2日益广泛的分子功能，从RNA稳定性和翻译的调控到对含有RNA-DNA杂交的R环结构有害积累的抑制。我们还强调了ataxin-2更广泛的生理作用，如在细胞代谢和昼夜节律调控中的作用。最后，我们讨论来自临床重点研究的见解，以阐明ataxin-2的分子和生理作用在各种人类疾病中的影响。我们预计，破译ataxin-2的基本功能将揭示帮助治愈或控制使人衰弱和致命的人类疾病的独特方法。
